Appendectomy and the risk of developing ulcerative colitis or Crohn''s disease: results of a large case-control study. South Limburg Inflammatory Bowel Disease Study Group

Copper amine oxidase from lentil seedlings was shown to be able to catalyze the oxidative deamination of the indoleamines tryptamine, 5-hydroxytryptamine, and 5-methoxytryptamine. These compounds showed saturation kinetics with Km values as normal substrates, but their oxidation led to irreversible loss of enzyme activity suggesting a covalent interaction with the enzyme, most probably through its cofactor 6-hydroxydopa (2,4,5-trihydroxyphenylalanine). These indoleamines acted as irreversible inhibitors of the enzyme only in the absence of oxygen but they brought about changes in the electronic spectra of the enzyme both in aerobiosis and in anaerobiosis. This study reports on the mechanism by which these compounds inhibit lentil amine oxidase which involves first the oxidation of indoleamines bound to 6-hydroxydopa followed by the formation of an irreversible covalent derivative. The same inhibitory mechanism could possibly lead to inactivation of mammalian amine oxidases involved in serotonin neurotransmitter metabolism in conditions of ischemia or hypoxia.     

Diagnosis by a waiter and a Mars explorer

This paper shows how state-of-the-art state estimation techniques can be used to provide efficient solutions to the difficult problem of real-time diagnosis in mobile robots. The power of the adopted estimation techniques resides in our ability to combine particle filters with classical algorithms, such as Kalman filters. We demonstrate these techniques in two scenarios: a mobile waiter robot and planetary rovers designed by NASA for Mars exploration.     

A comparison of the predictive values of the Salmonella/microsome mutation and BHK21 cell transformation assays in relation to dyestuffs and similar materials

A group of 22 dye-related compounds were selected for testing in two short-term predictive tests for carcinogenicity. The group of compounds was made up of nine established animal carcinogens and 13 chemicals for which there was substantial evidence of non-carcinogenicity. The materials were coded and used to assess the predictive value of the Salmonella/microsome reverse mutation assay and the BHK21 cell transformation test. The overall predictive value with these compounds obtained for the Salmonella microsome reverse mutation assay was 86% and it is concluded that because of the good predictive value and the relative ease of experimental procedure, the Salmonella mutation assay is a useful first step in any proposed series of toxicological bioassays for the identification of genotoxic agents in the dyestuffs industry.The cell transformation test on the other hand was difficult to conduct and interpret. The interpretation of the coded data as judged by the IRI scientists was that of the 22 'unknown' compounds, eight results were judged to be correct, six were wrong and seven were doubtful. However, when the same data were re-evaluated uncoded by ICI staff, 15 results were judged to be correct and six were wrong. These results serve to exemplify the difficulties encountered with cell transformation assays and it is concluded that the system should not be used as a routine test for dyestuffs and related compounds.     

The A-kinase anchoring domain of type IIalpha cAMP-dependent protein kinase is highly helical

Subcellular localization of the type II cAMP-dependent protein kinase is controlled by interaction of the regulatory subunit with A-Kinase Anchoring Proteins (AKAPs). This contribution examines the solution structure of a 44-residue region that is sufficient for high affinity binding to AKAPs. The N-terminal dimerization domain of the type IIalpha regulatory subunit of cAMP-dependent protein kinase was expressed to high levels on minimal media and uniformly isotopically enriched with 15N and 13C nuclei. Sequence-specific backbone and side chain resonance assignments have been made for greater than 95% of the amino acids in the free dimerization domain using high resolution multidimensional heteronuclear NMR techniques. Contrary to the results from secondary structure prediction algorithms, our analysis indicates that the domain is highly helical with a single 3-5-residue sequence involved in a beta-strand. The assignments and secondary structure analysis provide the basis for analyzing the structure and dynamics of the dimerization domain both free and complexed with specific anchoring proteins.     

New pathway of heparan sulphate degradation. Iduronate sulphatase and N-sulphoglucosamine 6-sulphatase act on the polymer chain prior to depolymerisation by a N-sulpho-glucosaminidase and glycuronidases in the mollusc Tagelus gibbus

In current clinical practice, it is important to be able to evaluate the evidence supporting each of our actions. Physicians can no longer rely on tradition or habit; however, with the increasing number of journals available, it is impossible for the practicing clinician to keep abreast of all the relevant literature. One valuable method of gathering and summarizing the latest information and opinions is the use of round tables and consensus conferences. Published reports of round table and consensus conference findings can be invaluable in guiding the clinician.     

Stewardship: the distinguishing characteristic of not-for-profit health care

In 1995 the French Academy of Science published a report on 'Problems associated with low doses of ionising radiation'. This report aroused interest among French-speaking scientists and a translation in English was published a year later. The report pointed out that an important issue in radioprotection was not whether to accept or reject the linear no-threshold model but rather to test its validity. The aim of this review is to analyse the report and its recommendations, and to briefly indicate the progress which has been made and the questions which remain open. Three areas of the report are covered in this review: DNA repair, carcinogenesis and epidemiological data.     

Immunoreactivity of apolipoprotein B-100 and binding to LDL-receptor of phospholipase A2-treated low density lipoproteins

Lipid--protein particles were obtained by treatment of low density lipoproteins (LDL) with phospholipase A2 from bee venom. Under these conditions, half of the phosphatidylcholine (PC) of LDL was changed to lysophosphatidylcholine (LPC). At the same time, the composition of other lipids and the apoprotein structure were unaffected. Three monoclonal antibodies (MAbs) against various apo B epitopes were used to test immunoreactivity of phospholipase A2-treated LDL (pl-LDL). The apo B epitope interacting with MAb 4C11 (amino acid residues 2377-2658) showed significantly decreased immunoreactivity. Increase in MAb 4C11 binding was demonstrated to depend on oxidation degree of LDL. Thus, changing of half of PC to LPC modified apo B translocation in the lipoprotein globule in an opposite manner as compared with changes induced by oxidative modification. A minor increase in immunoreactivity of pl-LDL with 1D1 MAb against a large middle part of apo B (residues 1297-3249) may be due to the effect of the change of surface lipid composition on the extent of immersion of apo B into the hydrophobic phase. No changes in the interaction of pl-LDL with MAb 2G8 (residues 3748-4306) were observed in comparison with native LDL. This fact demonstrates that 50% phospholipolysis of LDL does not affect the expression of apo B C-terminal residues in pl-LDL. Twofold increase in pl-LDL affinity to immobilized LDL-receptor was shown in contrast to LDL. The data indicate that LPC accumulation in LDL results in better elimination of LDL from the blood stream than in case of accumulation of oxidative products.